This invention relates to radioimmunoassay methods and more particularly to radioimmunoassay methods for the in vitro determination from an unknown test blood sample of a normal soluble endogenous cytoplasmic protein, such as S-100, released into the blood in the course of neurological diseases and which is susceptible to separation from other proteins simultaneously released into the blood.
As is known, the nervous system contains a number of proteins unique to its various cellular elements. The cellular disruption of nervous tissue, by any pathogenic process or by neurological diseases, results in the release of normal soluble endogeneous cytoplasmic proteins into the cerebral extracellular fluid and ultimately to other body fluids including the cerebrospinal fluid (CSF) and blood (serum and plasma). Representative small molecular weight, soluble, proteins of this type normally present in reasonably high concentrations have been isolated for glial cells (S-100), neurons (14-3-2) and myelin (PLP). Following disruption of cell membranes, these proteins are released into the extracellular fluid in accordance with a time course and in quantities relative to the pathogenesis of the disease process. These proteins diffuse into the CSF and then the blood. The progression of the disease process is reflected by the blood plasma or serum levels of one or more of these protein antigens or markers. These protein antigens have the advantage of being stable and specific, not only for the brain, but for the cellular components in the brain. If the relative release of the various nervous system protein antigens could be followed, it would make it possible to deduce the kind of destructive process occurring in the course of neurological diseases. Information of this type would permit the diagnosis, evaluation of severity and rate of progression of neurological diseases that result in cellular damage.
A need has existed, therefore, for practical means for the in vitro determination from an unknown test blood sample of a normal soluble endogenous cytoplasmic protein, such as S-100, released into the blood in the course of neurological diseases. Such a determination would be a great aid to the clinician in more precisely evaluating the extent of actual damage in strokes or other neurological disorders, especially early in the course when the clinical picture is frequently obscured by neurological disfunction resulting from inflammation and edema.